Repair of tooth-supporting structures destroyed by the chronic inflammatory disease periodontitis is a major goal of oral reconstructive therapy. We propose to develop a novel scaffolding system that can deliver regenerative agents to periodontal defects. This system consists of a nano-fibrous polymer scaffold modified with bone mineral-mimicking apatite containing microspheres for delivery of bioactive molecules such as bone morphogenetic protein-7 (BMP-7). It is anticipated that this scaffolding/factor delivery system will promote periodontal regeneration at the defect site by providing an environment for enhancing adhesion, migration, and differentiation of putative cells such as osteoblasts, cementoblasts, and periodontal ligament (PDL) fibroblasts. Moreover, this scaffolding delivery system will allow for permeation of nutrients, metabolites, and signaling molecules required for three dimensional (3D) tissue neogenesis. This exploratory research project will focus on development of the scaffolding/factor delivery system and on testing the feasibility of this novel method for use in treatment of periodontal defects. The following specific aims are designed to generate preliminary data to determine the strength of this approach for periodontal tissue engineering. Specific Aim 1. Design nano-fibrous scaffolds with interconnected spherical macropores and modified with bone mineral-like apatite. Specific Aim 2. Integrate microspheres containing BMP-7 into nano-fibrous scaffolds and evaluate the bioactivity and release kinetics of BMP-7 in vitro. Accomplishing these specific aims will generate critical preliminary data and provide vital information as to the appropriate scaffolding/factor delivery system for use in designing optimal periodontal regenerative therapies. This knowledge will enable us to develop a predictable biomimetic scaffold for in vivo application and will be the basis for our planned R01 investigation. [unreadable] [unreadable]